PI(3)P plays an essential role in multiple endocytic trafficking processes and autophagy.The class Ⅲ Vps34/Beclin 1/Atg14 PI(3)P kinase complex has been shown to be essential for autophagy, acting as a node for integrating nutrient status and growth factors into the autophagic machinery.The role of the class Ⅱ PI(3)P kinase in autophagy, and the mechanisms that control its activity, are still poorly understood.Here we identified a novel gene, susr-1 ((S)(u)ppressor of (S)QST-1 in (r)pl-43 mutants), that negatively regulates class Ⅱ PI(3)K activity.In susr-1 mutants, PI(3)P levels and autophagy activity are increased, both of which depend on the class Ⅱ PI(3)P kinase PIKI-1.Loss of function of susr-1 greatly ameliorates multiple neurodegenerative disease models, including expanded glutamine stretch, α-synuclein and β-amyloid.Our study demonstrates a role for the class Ⅱ PI(3)P kinase in autophagy regulation.