ATL2 (atlastin GTPase 2) is a membrane-anchored dynamin-like GTPase that mediates GTP-dependent fusion of endoplasmic reticulum (ER) membranes, maintaining the continuous ER network and forming three-way junctions where ER tubules intersect 1. The fusion mechanism involves homodimer formation through G domains upon GTP binding, followed by conformational tightening of the three-helix bundle regions that pulls membranes together, with subsequent GTP hydrolysis and dimer disassembly completing the cycle 2. ATL2 exists as multiple splice isoforms with divergent regulatory properties; the major isoform ATL2-1 is autoinhibited by its C-terminal α-helix, while neuronal isoforms show full fusion activity 1. All human atlastins, including ATL2, are sufficient to drive liposome fusion with physiological ER lipid composition 3. Beyond ER morphology, ATL2/3 regulate ULK1 complex targeting to the ER to initiate autophagy 4. Clinically, high ATL2-2 expression associates with worse prognosis in estrogen-receptor-positive breast cancer, correlating with MYC and E2F target pathway activation 5. Mutations in ATL genes are linked to hereditary sensory neuropathies and hereditary spastic paraplegia 2, highlighting ATL2's critical importance in cellular and neuronal health.