Atg2a, an essential core member of the autophagy machinery, facilitates lipid flow between tethered membranes, which is crucial for autophagosome formation [1]. Autophagy is a highly conserved cellular process maintaining cellular homeostasis, and Atg2a's role in lipid transfer during autophagosome biogenesis makes it significant in various biological processes and disease-related pathways. Genetic models, such as gene knockout models, can be valuable in further exploring its functions.

Knockdown of Atg2a in neuroblastoma-derived Neuro-2a (N2a) cells leads to significant accumulation of SQSTM1/p62 and MAP1LC3-II/LC3-II, indicating impaired autophagy. Atg2a deficiency does not affect autophagosome formation but reduces the colocalization of autophagosomal LC3 with late endosomal/lysosomal RFP-RAB7, suggesting impaired autophagosome-lysosome fusion [3]. Also, depletion of endosome-localized ANKFY1, an Atg2a-binding protein, phenocopies Atg2a/b depletion, impairing autophagosome growth and autophagy flux [2].

In conclusion, Atg2a is vital for autophagy, especially in processes like lipid transfer for autophagosome formation and autophagosome-lysosome fusion. Studies using gene knockout models in neural cells have revealed its role in maintaining normal autophagy function, providing insights into potential mechanisms underlying autophagy-related diseases.