This study expands the genotypic spectrum of LKPAT, indicates the potential pathogenesis of the <i>CLCN2</i> A506V variant, and provides valuable insights into further investigation into therapeutics of <i>CLCN2</i>-related leukoencephalopathy. Here, CLCN2 is linked to leukoencephalopathy with mild cerebellar ataxia and white matter edema.