Islr, also known as Meflin, contains an Ig-like domain, an LRR motif, and a transmembrane domain. It plays crucial roles in multiple biological processes, participating in various signaling pathways such as SPARC/p-ERK1/2, IGF1-PI3K/Akt-Foxo, and canonical Wnt signaling, and is important for muscle regeneration, muscle atrophy regulation, and insulin sensitivity [1,2,3,4]. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In adult mice, Islr deletion reduces muscle regeneration by decreasing the satellite cell pool and promoting their asymmetric division through the SPARC/p-ERK1/2 signaling pathway [1]. In myoblasts, Islr-silenced or Islr-overexpressed models show that Islr regulates myoblast differentiation, not proliferation, and can rescue dexamethasone-induced atrophy via the IGF/PI3K/AKT-FOXO signaling pathway [2]. In obese mice, Islr knockout increases insulin receptor alpha levels and insulin sensitivity in adipocytes, indicating its role in insulin resistance regulation [3]. Also, in adult mice, loss of Islr delays skeletal muscle regeneration as myoblasts fail to differentiate into mature myotubes due to defective canonical Wnt signaling, as Islr stabilizes Dishevelled-2 and prevents autophagy [4].

In conclusion, Islr is a key regulator in muscle-related processes and insulin sensitivity. Studies using Islr KO/CKO mouse models have provided insights into its role in muscle regeneration, atrophy, and insulin resistance-related diseases, helping to understand the underlying mechanisms and potentially offering new therapeutic targets.