TMEM88, a double-transmembrane protein, has emerged as a significant regulator in various biological processes. It is involved in mediating different signaling pathways, most notably the Wnt/β-catenin signaling pathway, and plays a crucial role in cell proliferation, differentiation, apoptosis, and tumor progression [1,2,3,4,5,6,7]. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions.

In bladder cancer, TMEM88 levels are lower, and its up-regulation decreases cell proliferative and invasive abilities by down-regulating the Wnt/β-catenin pathway, an effect reversed by suppressing GSK-3β or overexpressing β-catenin [3]. In zebrafish, loss of tmem88a/b leads to excessive expansion and failure of differentiation of pharyngeal arch artery progenitors due to enhanced cyclin D1 expression via aberrant Wnt signal activation [4]. Also, in zebrafish, tmem88a/b deficiency causes excessive accumulation of β-catenin in endodermal cells intended to differentiate into pharyngeal pouch progenitors, and suppressing Wnt/β-catenin signaling rescues the specification defects [7].

In conclusion, TMEM88 plays essential roles in multiple biological processes, especially in regulating cell proliferation and differentiation through the Wnt/β-catenin signaling pathway. The use of KO/CKO mouse models and other genetic models in zebrafish has provided insights into its role in diseases like cancer and in developmental processes, contributing to our understanding of these disease areas and potentially paving the way for new therapeutic strategies.