 P rogressive  E ncephalopathy with oedema,  H ypsarrhythmia and  O ptic atrophy (PEHO) is a rare, neurodegenerative disorder of unknown aetiology. Nahorski  et al . identify the first causative recessive mutation in  CCDC88A , which encodes the actin-binding protein Girdin. The phenotype and brain anatomy of the  Ccdc88a knockout mouse resemble those of human PEHO syndrome. 