TBC1D31 is a RAB GTPase-activating protein (GAP) and molecular adapter with dual roles in cilium biogenesis and cancer progression. In normal cellular function, TBC1D31 is essential for primary ciliogenesis through a centrosomal complex that includes the E3 ubiquitin ligase praja2 and protein kinase A (PKA) 1. Upon GPCR-cAMP stimulation, this complex catalyzes PKA-directed phosphorylation and ubiquitylation of the ciliopathy protein OFD1, promoting its proteasomal degradation—a process critical for proper cilium assembly and morphology 1. Mutations in TBC1D31 impair ciliogenesis and are associated with congenital anomalies of the kidney and urinary tract (CAKUT) 2, linking ciliary dysfunction to developmental disease. In cancer contexts, TBC1D31 functions as an oncogene. Genomic amplification of TBC1D31 at chromosome 8.13 promotes hepatocellular carcinoma through its RAB-GAP activity toward Rab22A, reducing endolysosomal trafficking and degradation of EGFR, thereby maintaining activated EGFR signaling 3. Similarly, elevated TBC1D31 expression in triple-negative breast cancer correlates with a glycolytic phenotype and poor prognosis 4, while polymorphisms in TBC1D31 predict ERBB2-driven mammary tumor susceptibility 5. Clinically, TBC1D31 overexpression confers lenvatinib resistance in hepatocellular carcinoma, suggesting therapeutic targeting potential 3.