Plxnb1, a member of the plexin family receptors, serves as the receptor for semaphorin 4D (Sema4D), participating in the semaphorin/plexin signaling pathway. This signaling is crucial in various biological processes, including the development of the nervous system, cell-cell interactions, and immune responses [1,2,3,5,6]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, have been instrumental in studying its functions.

In the context of idiopathic hypogonadotropic hypogonadism (IHH), six rare sequence variants in PLXNB1 were found in normosmic IHH patients. Functional analysis of one variant (p.R1031H) showed reduced membrane expression and impaired migration in GnRH cells, suggesting a role of PLXNB1 in IHH etiology [1]. In pediatric bipolar disorder (PBD), a rare homozygous loss-of-function PLXNB1 variant led to neurite outgrowth deficits in patient-derived cortical neurons, indicating that dysregulated PLXNB1 signaling may increase the risk of PBD [4]. In triple-negative murine breast carcinoma, PLXNB1-deficient mice showed reduced primary tumor growth and metastatic dissemination, along with a switch in tumor-associated macrophage polarization and enhanced CD8+ T lymphocyte infiltration. This indicates that PLXNB1 signaling controls the antitumor immune response in the tumor microenvironment [5].

In conclusion, Plxnb1, through its role in semaphorin/plexin signaling, is involved in multiple biological processes. Studies using KO/CKO mouse models have revealed its significance in diseases such as IHH, PBD, and breast cancer, providing insights into disease mechanisms and potential therapeutic targets.