A novel mutation in a large family causes a unique phenotype of Mucolipidosis IV

Involvement of the TRPML Mucolipin Channels in Viral Infections and Anti-viral Innate Immune Responses

“…Many patients carry mutations that introduce premature stop signals in MCOLN1, thus the TRPML1 protein is completely absent, or abnormally short and it lacks the ion conducting pore (13)(14)(15). Some patients show single point mutations in MCONL1 that maintain the open reading frame but lead to a incorrect location or to the production of a TRPML1 inactive form (11)(12)(13)(14)(16)(17)(18). TRPML2 mRNA is mainly detected in lymphocytes and other cells of the immune system (19).…”

A small molecule restores function to TRPML1 mutant isoforms responsible for mucolipidosis type IV

“…We focused on several MLIV causing point mutants described in the literature with either unknown subcellular localization (R403C, Y436C, V446L, V447P, S456L) 3,7,29,31,32 , or mutant isoforms reported to show partial localization on endosomes and lysosomes, that is, F408D, an in-frame mutant that lacks one amino acid, and F465L 7,30 (Fig. 1a, Supplementary Fig.…”

“…As a result, the TRPML1 protein is completely absent, or abnormally short and lacks the ion conducting pore between TMD5 and TMD6. Some patients however carry single point mutations which do not destroy the open reading frame 3,7,[29][30][31][32] . While some of these appear to be largely mislocalized, others retain a predominant lysosomal localization.…”