TBC1D30 is a Rab GTPase-activating protein that regulates insulin processing and secretion. The protein functions as a negative regulator of proinsulin secretion through its RabGAP domain, which modulates the secretory pathway by controlling Rab GTPase activity 1. Reduced TBC1D30 expression or impaired RabGAP domain function increases proinsulin secretion 1.8-2.6 fold in insulinoma cells, while elevated expression reduces secretion, indicating TBC1D30 suppresses inappropriate insulin cargo trafficking 1. The gene harbors a genome-wide association signal (rs150781447-T, Arg279Cys) linked to elevated plasma proinsulin levels, with the variant allele increasing proinsulin secretion 1. Calcineurin inhibitor tacrolimus suppresses TBC1D30 expression, contributing to impaired glucose-stimulated insulin secretion 2. Beyond endocrine function, TBC1D30 is hypermethylated in Barrett's esophagus and esophageal adenocarcinoma and associates with poor survival in breast and liver cancers when overexpressed 3, 4, 5. TBC1D30 appears involved in multiple secretory pathways through Rab regulation, with dysregulation contributing to metabolic disease and malignancy.