Structural mechanism of TRPC3 channel activation by the moonwalker mutation

TRPC3 is a receptor-activated, non-selective cation channel expressed in the cerebellum and is critical for the proper development and function of Purkinje cells 1 . A gain-of-function mutation of TRPC3, T561A, leads to impaired dendritic arborization of Purkinje cells and cerebellar ataxia, manifesting as a distinctive moonwalker gait abnormality in mice 1 . Additionally, TRPC3 has increasingly been recognized for its involvement in immune responses, cancer progression, and various cardiovascular and neurological disorders, further underscoring its potential as a therapeutic target 2 .