Phosphorylation of Parkin at serine 65 is essential for its activation .

Mutations in PINK1 and Parkin result in autosomal recessive Parkinson's disease (PD). Cell culture and studies have elaborated the PINK1-dependent regulation of Parkin and defined how this dyad orchestrates the elimination of damaged mitochondria via mitophagy. PINK1 phosphorylates ubiquitin at serine 65 (Ser65) and Parkin at an equivalent Ser65 residue located within its N-terminal ubiquitin-like domain, resulting in activation; however, the physiological significance of Parkin Ser65 phosphorylation in mammals remains unknown.