Atlastin-3 (ATL3)

Atlastin-3 (ATL3) is a membrane-anchored large GTPase belonging to the dynamin superfamily, responsible for mediating the GTP-dependent homotypic fusion of endoplasmic reticulum (ER) membranes[3][1]. Highly expressed in muscle tissue, ATL3 is essential for maintaining the continuous and dynamic network of the ER[3][1]. It acts as a key determinant of ER morphology by tethering and fusing opposing ER membranes, mechanisms driven by GTP binding and hydrolysis and timed by conformational changes in its GTPase and three-helix bundle domains[2][6][4]. ATL3 additionally functions as a receptor for ER-phagy by directly binding to the autophagy protein GABARAP and facilitating ER degradation during starvation conditions[5]. Mutations in ATL3 are associated with hereditary sensory neuropathy type I (HSN1F), as well as other peripheral neuropathies, implicating its critical function in neuronal maintenance[5]. No drugs are known to specifically target ATL3, and its primary disease relevance is through loss-of-function mutations resulting in disrupted ER dynamics and ensuing neurodegeneration rather than as a classical pharmacological receptor or enzyme target[5][1].

Other names

Atlastin-3ATL3AT3ATL-3DKFZP564J0863HSN1Fatlastin GTPase 3

Not established for direct therapeutic targeting; mechanistic actions include GTP-dependent dimerization and membrane fusion via homotypic ER fusion