| Aspect | Key points |
|---|---|
| Identity/domains | - Verified target: human **ATG2A** (UniProt **Q2TAZ0**), autophagy-related protein 2 homolog A; member of the **ATG2/RBG bridge-like lipid transfer family** with a rod-like architecture (pqac-00000004, pqac-00000012, pqac-00000014)  <br>- Contains an **N-terminal chorein/N_chorein** lipid-transfer module and a long hydrophobic groove/cavity consistent with bulk phospholipid transport (pqac-00000004, pqac-00000006)  <br>- Has a **C-terminal CLR** with amphipathic helices for membrane association, plus conserved **LIR motifs** and ATG9-binding regions including an S2 site around aa 1760–1779 (pqac-00000000, pqac-00000004, pqac-00000008) |
| Core molecular function | - Primary function is **bulk/bridge-like lipid transfer** to support **phagophore expansion** during autophagosome biogenesis (pqac-00000002, pqac-00000010, pqac-00000014)  <br>- Also acts as a **membrane tether** at ER–phagophore contact sites; purified ATG2 proteins tether highly curved membranes and transfer lipids between tethered membranes in vitro (pqac-00000000, pqac-00000006)  <br>- Outside canonical autophagosome growth, ATG2A can mediate **bridge-like phospholipid transport on lipid droplet monolayers**, affecting lipid droplet homeostasis (pqac-00000007) |
| Key interaction partners | - **WIPI4/WDR45** is a strong ATG2A partner that helps target ATG2A toward **PI3P-rich** autophagic membranes and enhances tethering/lipid transfer directionality (pqac-00000000, pqac-00000002)  <br>- **ATG9A/ATG9B** interact functionally and physically with ATG2A; the complex couples ATG2A lipid transfer to ATG9 scramblase activity and is essential for phagophore expansion (pqac-00000008, pqac-00000012, pqac-00000014)  <br>- **VMP1** and **TMEM41B** interact with the ATG2A N terminus at the ER side of the contact, while **ANKFY1** was identified in 2024 as an endosomal ATG2A-binding factor that promotes PI3P-dependent lipid transfer from endosomes to phagophores (pqac-00000001, pqac-00000006, pqac-00000012) |
| Subcellular localization | - Enriched at **phagophore extremities/rims** and **ER–phagophore membrane contact sites**, including omegasome-associated regions during autophagosome formation (pqac-00000002, pqac-00000005)  <br>- Localizes with **ATG9** and **WIPI4** on early autophagic membranes, with coincidence binding to PI3P and ATG9 helping recruitment/specificity (pqac-00000000, pqac-00000002)  <br>- Additional pools localize to **lipid droplets** and, in 2024 work, to interfaces between **PI3P-positive endosomes and phagophores** via ANKFY1 (pqac-00000005, pqac-00000006, pqac-00000007) |
| Mechanistic model | - Current model: ATG2A forms a **lipid bridge/highway** between donor and acceptor membranes, transferring lipids from the **ER** to the expanding phagophore while scramblases equilibrate lipids across bilayer leaflets (pqac-00000003, pqac-00000012)  <br>- Directionality/specificity is thought to arise from the combination of **ATG2A with WIPI4, ATG9A, VMP1, and TMEM41B**, with local ER lipid synthesis proposed to help drive net lipid flow (pqac-00000001, pqac-00000012)  <br>- A 2024 extension of this model proposes that **endosomes can also donate PI3P and other lipids** to phagophores through **ANKFY1-assisted ATG2A transfer** (pqac-00000006, pqac-00000015) |
| Quantitative/experimental data | - ATG2A is described as a rod-like protein of about **~20 nm** length; ATG2A and ATG2B share **44.5% identity** (pqac-00000004)  <br>- Purified ATG2A binds/tethers **~30 nm small unilamellar vesicles** better than **~100 nm large unilamellar vesicles**, consistent with preference for highly curved/packing-defective membranes (pqac-00000006)  <br>- In lipid-droplet assays, donor artificial LDs had median diameter **~165 nm (IQR 129–211 nm)** and monolayer-containing donors accelerated lipid mixing by **at least 4-fold** relative to comparable ~100 nm bilayer liposomes; transport-dead ATG2A failed to rescue LD accumulation in knockout cells (pqac-00000007) |
| Recent 2023-2024 developments | - **2023** reviews consolidated ATG2A as a central **RBG-family bulk lipid transporter/tether** in autophagosome biogenesis, integrating structural and biochemical findings into a more unified bridge-transfer model (pqac-00000002, pqac-00000010)  <br>- **2023** preprint work linked ATG2A bridge-like transport directly to **lipid droplet accumulation/homeostasis**, expanding its biology beyond phagophore growth (pqac-00000007)  <br>- **2024** studies added new partners and contexts: **ANKFY1** as an endosomal recruiter/promoter of ATG2A-mediated transfer, and **ATG9B** as a tissue-specific scramblase that can also complex with ATG2A (pqac-00000006, pqac-00000012) |
| Disease/physiology links | - ATG2A supports fundamental **cellular lipid homeostasis** through autophagosome biogenesis and lipid-droplet regulation, so perturbation is expected to impact stress adaptation and metabolism (pqac-00000007, pqac-00000010)  <br>- Reviews of ER membrane-contact-site biology and autophagy genes place ATG2-family bridge lipid transport within broader mechanisms relevant to **neurodegeneration and human disease**, although ATG2A-specific Mendelian disease evidence remains less developed than for some partner proteins (pqac-00000003, pqac-00000010)  <br>- Loss of ANKFY1 phenocopied ATG2A/B depletion for impaired autophagosome growth and reduced flux, underscoring the physiological importance of ATG2A-mediated membrane supply routes (pqac-00000006) |
| Non-canonical autophagy/lysosome damage | - In **2023**, lysosome damage was shown to trigger **CASM/non-canonical autophagy-dependent engagement of ATG2**, linking ATG2A/B to lysosomal stress responses beyond canonical phagophore expansion (pqac-00000011)  <br>- In ATG2A/B double-knockout reconstitution experiments, ATG2–LC3 interaction during lysosome damage required the **ATG2A LIR** rather than the WIPI4-binding region, supporting a distinct ATG8-dependent recruitment mode (pqac-00000011)  <br>- ATG2A and ATG2B were recovered on damaged lysosomes, and the study proposed a role in **lysosome repair** alongside other damage-response pathways (pqac-00000011) |


*Table: This table summarizes the verified identity, molecular function, partners, localization, and recent mechanistic advances for human ATG2A (UniProt Q2TAZ0). It is useful as a compact evidence map linking ATG2A's lipid-transfer role to canonical autophagy, lipid droplet biology, and lysosomal damage responses.*