Wnt5b, a member of the WNT family closely related to Wnt5a, is crucial for cell migration, proliferation, and differentiation in many cell types [1]. It signals through the non-canonical β-catenin-independent pathway and often acts as an antagonist of canonical WNT signaling [1]. Wnt5b is involved in various physiological and pathological processes, making it a significant gene in biological research.

In osteosarcoma, Wnt5b is highly expressed in tumors, correlating with metastasis, histologic subtype, and reduced survival [2]. It enriches in stem cells, promotes stem-like properties such as sphere-forming, proliferation, migration, and chemoresistance to methotrexate, and increases lung and liver metastasis in vivo [2].

In non-small cell lung cancer (NSCLC), Wnt5b overexpression correlates with advanced TNM stage, lymph node metastasis, and poor prognosis, and it promotes the malignant phenotype of NSCLC cells via the FZD3-DVL3-RAC1-PCP-JNK pathway [3].

In Pacific white shrimp, Wnt5b expression is regulated by the IMD-Relish and JAK-STAT pathways, is suppressed upon bacterial infection, and plays a negative role in antibacterial response [4].

In colorectal cancer, oncogenic KRAS activates TFCP2, which upregulates Wnt5b, contributing to the transformation of carcinoma-associated fibroblasts into lipid-rich CAFs that promote angiogenesis [5].

In bone cancer pain, Wnt5b/Ryk-mediated membrane trafficking of P2X3 receptors via CaMKII activation leads to peripheral sensitization and pain [6].

In summary, Wnt5b is essential for multiple biological processes and is involved in various diseases, including osteosarcoma, NSCLC, and colorectal cancer, as well as in antibacterial response and bone cancer pain. Studies using different models have revealed its diverse functions, highlighting its potential as a therapeutic target in these disease areas.