S100A6, also called calcyclin, is a Ca2+-binding protein belonging to the S100 protein family. It has diverse functions related to the cytoskeleton, cell stress, proliferation, and differentiation. S100A6 interacts with many proteins in a Ca2+-dependent manner, and its expression is regulated by transcription factors and epigenetic modifications. It plays a crucial role in various biological processes and is a potential biomarker and therapeutic target in multiple diseases [1,2,3,4,6].

In liver cancer, S100A6 secreted from tumor cells promotes lymphangiogenesis through the RAGE/NF-κB/VEGF-D pathway, and overexpression in tumor cells enhances their migration and invasion, suggesting its dual role in promoting lymphatic metastasis [5]. In autoimmune encephalitis, S100A6 is hypomethylated, promotes B lymphocyte infiltration through the blood-brain barrier, and its antibodies can counteract this effect, indicating its potential as a treatment target [7]. In intervertebral disc degeneration, S100A6 expression increases, promoting nucleus pulposus cell apoptosis via the Wnt/β-catenin signaling pathway, making it a promising therapeutic target [8].

In conclusion, S100A6 is involved in multiple cellular functions and disease-related processes. Its role in promoting lymphatic metastasis in liver cancer, participating in autoimmune encephalitis, and contributing to intervertebral disc degeneration, as revealed through in vivo-like studies, highlights its importance in these disease areas. Understanding S100A6 can provide new insights for disease diagnosis, prognosis, and treatment.