RPH3AL (rabphilin-3A-like) is a Rab GTPase effector protein involved in regulated exocytosis, particularly in endocrine cells. Mechanistically, RPH3AL acts as a dual effector that cooperatively binds both Rab2a and Rab27a in a GTP-dependent manner, orchestrating the transition from granule maturation to exocytosis 1. In pancreatic β-cells, the ternary Rab2a-Noc2-Rab27a complex localizes on immature perinuclear granules and is essential for glucose-stimulated insulin secretion 1. Clinically, RPH3AL functions as a putative tumor suppressor. Loss of heterozygosity (LOH) at the RPH3AL locus (17p13.3) is detected in approximately 66% of breast cancers and is significantly associated with nodal metastasis, advanced stage, large tumor size, and poor patient survival 2. Similarly, RPH3AL mutations have been identified in colorectal cancers, though in only a minority of cases 3. Circulating autoantibodies against RPH3AL are prevalent in 73% of colorectal cancer patients versus 16% of healthy controls, suggesting potential diagnostic utility 4. Additionally, differential DNA methylation of RPH3AL has been observed in male infertility and aortic aneurysm pathology 56, indicating broader disease relevance beyond cancer.