Galnt18-KO Mouse

GALNT18, also known as polypeptide N-acetylgalactosaminyltransferase 18, is involved in mucin-type O-glycosylation. Unlike most enzymes in this family located in the Golgi apparatus, it is predominantly on the endoplasmic reticulum (ER) and has no in vitro catalytic activity for this glycosylation. It plays a crucial role in maintaining ER homeostasis and protein O-glycosylation, and is thus important for various biological processes [4].

In rheumatoid arthritis patients, the GALNT18-CC genotype is associated with better EULAR response, remission, low disease activity (LDA) and DAS28 improvement when treated with tocilizumab [1]. In Chinese children, the rs274503 polymorphism in ZBED5/GALNT18 is associated with the risk of idiopathic clubfoot, with the G allele increasing the bilateral case rate [2]. Also, in lupus patients, demethylation of a CpG site within GALNT18 is related to the development of active lupus nephritis [3].

In conclusion, GALNT18 is essential for ER homeostasis and O-glycosylation. Studies in human disease conditions such as rheumatoid arthritis, idiopathic clubfoot, and lupus nephritis have revealed its associations with disease susceptibility and treatment response, highlighting its significance in understanding these disease mechanisms and potentially guiding personalized treatment strategies.