GOLGA2, also known as GM130, is a cis-Golgi matrix protein. It plays a crucial role in glycosylation and protein transport in the secretory pathway. GOLGA2 is also involved in vesicle tethering, cell proliferation, and autophagy, and is essential for the assembly of the Golgi apparatus as a single complex [1,2,4,5]. Genetic models, such as gene knockout in mice and zebrafish, have been valuable in studying its functions [5].

In GOLGA2 knockout mice, deletion of GOLGA2 induces autophagy along with Golgi disruption. This autophagy induction leads to fibrosis in the lung and liver, accompanied by a reduction in subcellular lipid storage [3]. In a human patient with a homozygous loss-of-function mutation in GOLGA2, a neuromuscular disorder characterized by developmental delay, seizures, progressive microcephaly, and muscular dystrophy was observed. Knockdown of golga2 in zebrafish recapitulated the human phenotype of severe skeletal muscle disorganization and microcephaly [5]. A second consanguineous family with bi-allelic loss-of-function mutations in GOLGA2 also presented with microcephaly, seizures, and myopathy [6].

In conclusion, GOLGA2 is essential for Golgi function, autophagy regulation, and normal development. The GOLGA2 knockout models in mice and zebrafish, as well as human cases with GOLGA2 mutations, have revealed its role in fibrosis and neuromuscular disorders, providing insights into the underlying mechanisms and potential therapeutic targets for these disease areas.