The cytosolic PNGase (peptide:N-glycanase), also known as peptide-N4-(N-acetyl-β-glucosaminyl)-asparagine amidase, is a well-conserved deglycosylation enzyme (EC 3.5.1.52) which catalyzes the non-lysosomal hydrolysis of an N(4)-(acetyl-β-d-glucosaminyl) asparagine residue (Asn, N) into a N-acetyl-β-d-glucosaminyl-amine and a peptide containing an aspartate residue (Asp, D). This enzyme (NGLY1) plays an essential role in the clearance of misfolded or unassembled glycoproteins through a process named ER-associated degradation (ERAD). Accumulating evidence also points out that NGLY1 deficiency can cause an autosomal recessive (AR) human genetic disorder associated with abnormal development and congenital disorder of deglycosylation. In addition, the loss of NGLY1 can affect multiple cellular pathways, including but not limited to NFE2L1 pathway, Creb1/Atf1-AQP pathway, BMP pathway, AMPK pathway, and SLC12A2 ion transporter, which might be the underlying reasons for a constellation of clinical phenotypes of NGLY1 deficiency. The current comprehensive review uncovers the NGLY1’ssdetailed structure and its important roles for participation in ERAD, involvement in CDDG and potential treatment for NGLY1 deficiency.

The gene cell migration inducing hyaluronidase 1 (CEMIP) is on chromosome 15q25 and codes for a 150-kDa protein with an N-terminal secretion signal, a G8 domain, 2 GG domains, and several repeats. It was first described as a specific protein in the inner ear relating to nonsyndromic hearing loss. Recently, increasing research detected its association in various cancers, determining the progression, metastasis, and prognosis by influencing the proliferation and invasion of the cells. This relation is accomplished through various interacting pathways, such as the Wnt/β-catenin signaling pathway and the epidermal growth factor receptor signaling pathway. Thus, CEMIP could be a novel and potential focus for tumor diagnosis and treatment, but further studies on the regulatory role of CEMIP in vivo and in vitro are still needed. Herein, we summarize the process in recent studies of CEMIP, especially in cancer research. Abbreviations: AMPK = AMP-activated protein kinase, BiP = binding immunoglobulin, CA19-9 = cancer antigen 19-9, CASC19 = cancer susceptibility 19, CCA = cholangiocarcinoma, CDH23 = cadherin-related 23, CEMIP = cell migration-inducing hyaluronidase 1, CRC = colorectal cancer, ECM = extracellular matrix, EGF = epidermal growth factor, EGFR = epidermal growth factor receptor, EMT = epithelial-mesenchymal transition, Fzd = frizzled, GJB2 = gap junction protein beta 2, GSK3β = glycogen synthase kinase 3β, HUGE = human unidentified gene-encoded, MEK1 = mitogen-activated protein kinase 1, NADPH = reduced nicotinamide adenine dinucleotide phosphate, NF-κB = nuclear factor-κB, PKC = protein kinase C, PP2A = protein phosphatase 2A, PTP4A3 = protein tyrosine phosphatase type IVA member 3, SLC26A4 = Solute carrier family 26 member 4, TCF/LEF = T-cell factor/lymphoid enhancer factor, TMEM2L = transmembrane protein 2-like, TUG1 = taurine-upregulated gene 1, WBP11 = WW domain binding protein 11, ZO1 = Zona occludens 1.

Background: Abnormal white matter is a common neurobiological change in bipolar disorder, and dysregulation of myelination in oligodendrocytes is the cause. Transmembrane protein 108 (Tmem108), as a susceptible gene of bipolar disorder, is expressed higher in oligodendrocyte lineage cells than any other lineage cells in the central nervous system. Moreover, Tmem108 mutant mice exhibit mania-like behaviors, belonging to one of the signs of bipolar disorder. However, it is unknown whether Tmem108 regulates myelination of the oligodendrocytes.Results: Tmem108 expression in the corpus callosum decreased with the development, and hypermyelination of the corpus callosum was found in Tmem108 mutant mice, accompanying high expression of myelin basic protein. Strikingly, both oligodendrocyte progenitor cell proliferation and oligodendrocyte myelination were enhanced in the mutant mice. Furthermore, the mutant mice exhibited mania-like behavior after acute restraint stress and were susceptible to drug-induced epilepsy. Conclusions: Tmem108 inhibited oligodendrocyte progenitor cell proliferation and mitigated oligodendrocyte maturation in the corpus callosum, which may also provide a new role of Tmem108 involving bipolar disorder pathogenesis.

The cytosolic PNGase (peptide:N-glycanase; Png1 in yeast; NGLY1/Ngly1 in human/mice), also known as peptide-N4-(N-acetyl-beta-glucosaminyl)-asparagine ami-dase, is a well-conserved deglycosylation enzyme (EC 3.5.1.52) which catalyzes the non-lysosomal hydrolysis of an N(4)-(acetyl-β-D-glucosaminyl) asparagine residue into N-acetyl-β-D-glucosaminylamine and a peptide containing an aspartate residue. This enzyme (NGLY1) plays essential roles in clearance of misfolded or unassembled gly-coproteins through a process named ER-associated degradation (ERAD). Accumulating evidence also points out that NGLY1 deficiency can cause an autosomal recessive hu-man genetic disorder associated with abnormal development and congenital disorder of deglycosylation. In addition, the loss of NGLY1 can affect multiple cellular pathways, including but not limited to NFE2L1 pathway, Creb1/Atf1-AQP pathway, BMP path-way, AMPK pathway, and SLC12A2 ion transporter, which might be the underlying reasons for a constellation of clinical phenotypes of NGLY1 deficiency. The current comprehensive review indeed uncovers the detailed NGLY1’s structure and its im-portant roles for participation in ERAD, involvement in CDDG and potential treatment for NGLY1 deficiency.