Rab27A

Rab27A is a member of the Rab family of small GTPases, proteins that regulate vesicular trafficking within the cell. Like other Rab proteins, Rab27A cycles between an inactive GDP-bound form and an active GTP-bound form and is anchored to membranes through C-terminal prenylation, allowing it to coordinate vesicle docking and fusion events on late endosomes, lysosome-related organelles, and secretory granules.

In melanocytes, Rab27A controls the transport and peripheral dispersion of melanosomes by forming a complex with melanophilin (Mlph) and myosin Va, guiding melanosomes to the cell periphery for proper pigment distribution.

In cytotoxic T lymphocytes and natural killer cells, Rab27A regulates exocytosis of cytolytic granules by interacting with effector proteins such as Munc13-4 (UNC13D) and related adaptors, enabling targeted secretion that mediates immune cell–mediated cytotoxicity.

Genetic and clinical significance: Mutations in the RAB27A gene cause Griscelli syndrome type 2, a rare autosomal recessive disorder characterized by hypopigmentation with silver hair and immune deficiency due to defective lytic granule exocytosis. Affected individuals may experience increased susceptibility to infections and, in some cases, hemophagocytic lymphohistiocytosis.

Rab27A is thus a key regulator of vesicle trafficking in pigment cells and cytotoxic lymphocytes, with disruptions leading to combined pigmentary and immune system defects.