Rab-like protein 3

Rab-like protein 3 (RABL3) is a small GTPase that regulates KRAS signaling and cell proliferation, and serves as a regulator of prenylation for KRAS and other small GTPases (UniProt: Q5HYI8). It plays a critical role in ciliary vesicle formation through interaction with Rab11 at the mother centriole, a process essential for early ciliogenesis and dependent on its GTP-binding capacity. RABL3 is also required for lymphocyte development and function.

RABL3 is primarily studied in the context of pancreatic cancer, where mutations have been associated with pancreatic cancer susceptibility (UniProt: Q5HYI8, MIM 618680). The protein's roles in cell proliferation regulation and vesicular trafficking suggest potential involvement in broader cellular homeostasis pathways.

In Alzheimer's disease, RABL3 is significantly downregulated in post-mortem AD brain tissue relative to age-matched controls (Chaparral AD proteomics, mean log2FC −0.24). This reduction may affect ciliary maintenance, vesicular trafficking, or KRAS-dependent signaling in neuronal contexts, though the functional consequences of this downregulation in AD pathophysiology remain to be clarified.