The　macroautophagy/autophagy　proteins　ATG2A　and　ATG2B　transfer　lipids　for　phagophore　membrane　growth.　They　also　form　stable　complexes　with　WDR45　and　WDR45B.　Our　previous　study　demonstrated　that　WDR45　and　WDR45B　mediate　autophagosome-lysosome　fusion　in　neural　cells.　Given　the　defective　autophagosome　formation　in　cells　lacking　both　ATG2s,　their　role　in　later　autophagy　stages　is　hard　to　explore.　Here,　we　report　that　in　neuroblastoma-derived　Neuro-2a　(N2a)　cells,　knocking　down　(KD)　Atg2a,　but　not　Atg2b,　results　in　significant　accumulation　of　SQSTM1/p62　and　MAP1LC3-II/LC3-II,　indicating　impaired　autophagy.　Atg2a　deficiency　does　not　affect　autophagosome　formation,　but　reduces　colocalization　of　autophagosomal　LC3　with　late　endosomal/lysosomal　RFP-RAB7,　suggesting　impaired　autophagosome-lysosome　fusion.　ATG2A　interacts　with　the　SNARE　proteins　STX17,　SNAP29,　and　VAMP8,　facilitating　their　assembly.　Overexpression　of　ATG2A　partially　rescues　the　autophagosome-lysosome　fusion　defects　in　Wdr45-　and　Wdr45b-deficient　cells.　ATG2　and　another　tether　protein,　EPG5,　function　partially　redundantly　in　mediating　autophagosome-lysosome　fusion.　Thus,　ATG2A　plays　a　key　role　in　neural　autophagy　by　tethering　autophagosomes　with　lysosomes　for　fusion.Abbreviations:　AAV:　adeno-associated　virus;　ATG2Ar:　RNAi-resistant　ATG2A;　Baf:　bafilomycin　A1;　co-IP:　co-immunoprecipitation;　CQ:　chloroquine;　DKD:　double　knockdown;　DKO:　double　knockout;　ER:　endoplasmic　reticulum;　KD:　knockdown;　KO:　knockout;　MIL:　membrane-impermeable　Halo　ligand;　MPL:　membrane-permeable　Halo　ligand;　N2a:　Neuro-2a;　NC　negative　control;　PG:　phagophore;　PtdIns3K:　phosphatidylinositol　3-kinase;　PtdIns3P:　phosphatidylinositol-3-phosphate;　TEM:　Transmission　electron　microscopy;　TM:　transmembrane　domain;　WT:　wild-type.