IL-40, also known as C17orf99, is an intriguing cytokine that has recently been discovered as a novel protein secreted by B cells. It is expressed in specific mammals and is derived from the bone marrow and fetal liver. While its primary role is in maintaining B cell homeostasis and promoting B cell maturation and development, IL-40 also plays a crucial role in humoral immunity, particularly in the production of antibodies, with a specific emphasis on IgA production. As well as there are relationship between IL-40 and neutrophil extracellular traps externalization (NETosis) markers. In addition to its involvement in normal B cell functions, IL-40 has been found to have significant implications in the pathogenesis of several diseases. Research has linked IL-40 to rheumatoid arthritis, hepatocellular carcinoma, non-Hodgkin B cell lymphoma, Sjogren’s syndrome, pSS-associated NHL, autoimmune thyroid disease, Type 2 diabetes mellitus, ankylosing spondylitis, chronic obstructive pulmonary disease, and systemic lupus erythematosus. This suggests that IL-40 could potentially serve as a diagnostic or treatment biomarker for these conditions. However, despite these exciting findings, there is still much to be learned about IL-40. Further research is necessary to uncover additional properties and functions of this cytokine. Ongoing studies aim to elucidate the mechanisms by which IL-40 contributes to B cell biology and humoral immunity, as well as its role in disease pathogenesis. These investigations will help determine the potential therapeutic applications of IL-40 and its utility as a diagnostic marker. In this minireview, we aim to discuss the recent findings surrounding IL-40.