Myoferlin (MYOF), a member of the ferlin family, is a type II transmembrane protein with a single transmembrane domain at the carbon terminus [2]. It is involved in pivotal physiological functions related to numerous cell membranes, such as extracellular secretion, endocytosis cycle, vesicle trafficking, membrane repair, membrane receptor recycling, and secreted protein efflux [2]. MYOF is associated with multiple biological processes and diseases, and genetic models can be valuable for its study.

Mutations in the MYOF gene have been identified as a cause of hereditary angioedema with normal C1 esterase inhibitor gene (HAE-nl-C1-INH) [1,3]. In cancer research, MYOF is overexpressed in various cancers like colorectal, pancreatic, breast, melanoma, gastric, and non-small-cell lung cancer, and high expression is associated with high tumor invasion and poor clinical prognosis [2,4]. Functional studies in vitro using primary patient's skeletal muscle mesenchymal progenitor cells, including RNA sequencing and morphological studies, as well as in vivo zebrafish experiments, support the disease-causative role of a MYOF variant in limb-girdle type muscular dystrophy and cardiomyopathy [5]. A novel MYOF inhibitor, HJ445A, demonstrated superior antitumor efficacy in vivo, potently repressing the proliferation of gastric cancer cells and preventing their migration [6].

In summary, MYOF plays crucial roles in membrane-related physiological functions and is associated with diseases such as hereditary angioedema, various cancers, limb-girdle type muscular dystrophy, and cardiomyopathy. Model-based research, including in vitro and in vivo studies, has helped reveal these functions and associations, providing insights into disease mechanisms and potential therapeutic targets.