Gamma-aminobutyric acid receptor-associated protein (GABARAP)

Gamma-aminobutyric acid receptor-associated protein (GABARAP) is a ubiquitin-like cytosolic protein encoded by the GABARAP gene in humans. Originally identified as a protein interacting with the γ2 subunit of the GABA(A) receptor, GABARAP plays a central role in the intracellular trafficking and clustering of neurotransmitter receptors, particularly GABA(A) receptors, by linking them to the cytoskeleton. GABARAP is also recognized as a mammalian ortholog of yeast Atg8, functioning in autophagosome formation during autophagy and mediating the selective sequestration and degradation of cytosolic cargo. This protein is further involved in interactions with microtubules (e.g., tubulin), scaffold proteins (such as gephyrin), and autophagic receptors. Its structure includes a conserved ubiquitin-like core and N-terminal helices, supporting its roles in membrane dynamics, protein trafficking, and autophagy. Dysfunction or altered expression of GABARAP has been implicated in neurodegenerative and psychiatric disease models, principally through its regulation of synaptic receptor surface levels and cellular proteostasis. GABARAP is not a classical therapeutic target such as a receptor or enzyme but is instead considered a regulatory protein critical for both neural transmission and cellular homeostasis.

Other names

GABA(A) receptor-associated proteinFLC3BHT004MM46ATG8AGABARAP-aepididymis secretory sperm binding protein

Not a direct drug target; however, GABARAP modulates receptor trafficking and autophagy mechanisms. Experimental manipulation (such as knockdown or overexpression) alters GABAergic synaptic efficacy and autophagy function rather than being the point of direct drug action