PCMTD1 functions as a substrate recognition component of an ECS (Elongin BC-CUL5-SOCS-box protein) E3 ubiquitin ligase complex that mediates ubiquitination and proteasomal degradation of target proteins 1. The protein specifically binds the methyltransferase cofactor S-adenosylmethionine (AdoMet) through its N-terminal AdoMet binding motif, despite lacking methyltransferase activity 1. Mechanistically, PCMTD1 associates with Cullin-RING proteins Elongins B and C and Cul5 both in vitro and in human cells, functioning as an E3 ubiquitin ligase adaptor protein 1. Recent structural studies demonstrate that the PCMTD1 CRL complex specifically recognizes L-isoaspartyl residues when bound to AdoMet, providing an alternative maintenance pathway for proteins damaged by spontaneous L-isoaspartyl modification 2. Disease relevance includes associations with primary angle-closure glaucoma (PACG), where genetic variants in the PCMTD1-ST18 locus have been identified as susceptibility factors in genome-wide association studies 3. However, population-specific studies show variable associations, with some ethnic groups showing no significant association with PACG 45. The protein represents a novel mechanism for proteome maintenance through targeted degradation of age-related protein damage.