Atlastin-3

Atlastin-3 (ATL3) is a membrane-anchored GTPase that mediates GTP-dependent fusion of endoplasmic reticulum (ER) membranes, maintaining the continuous ER network architecture. The protein facilitates three-way junction formation where ER tubules intersect through a GTP-dependent mechanism involving homodimer assembly, membrane pulling, and subsequent disassembly upon GTP hydrolysis (UniProt: Q6DD88).

ATL3 is primarily associated with the secretory pathway and ER homeostasis. In addition to its housekeeping role, mutations in ATL3 cause hereditary sensory neuropathy 1F (HSN1F), an autosomal dominant condition characterized by distal sensory impairment and foot ulceration beginning in the second or third decade (UniProt: Q6DD88).

In Alzheimer's Disease, ATL3 is upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.44 across two subcellular fractions detected via TMT-labeled quantitative proteomics (Chaparral AD proteomics). This elevation suggests altered ER membrane dynamics or organellar stress responses may be relevant to AD pathophysiology.