Since dysregulation of clustered protocadherins is associated with a variety of neurological and neurodevelopmental diseases as well as mental disorders including autism spectrum disorder, bipolar disorder, Alzheimer’s disease, cognitive impairments, and schizophrenia (42, 43), our data on the key importance of the HUSH complex in protocadherin gene expression might provide new understanding on the epigenetic regulation of such diseases. Here, PCDH11X is linked to Alzheimer disease.