S100A6 (Calcyclin) is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are found in the cytoplasm and/or nucleus of a wide range of cells, where they modulate cell cycle progression and differentiation. S100A6 may stimulate Ca2+-dependent insulin release, prolactin secretion, and exocytosis, and it may also alter stress responses. In the brain, it is primarily expressed in neurons in the amygdala and entorhinal cortex, as well as in some astrocytes. S100A6 is overexpressed in neurodegenerative diseases including Alzheimer’s and amyotrophic lateral sclerosis (ALS, upregulation in astrocytes). Furthermore, chromosomal rearrangements and altered expression of this gene have been implicated in melanoma. In immunohistochemistry, S100A6 has cytoplasmic and nuclear positivity in most tissues throughout the body. References: PLoS One. 2017; 12(1): e0169760, PMID: 28068373; J Comp Neurol. 1999 Feb 8; 404(2):235-57, PMID: 9934997; Cardiovasc Psychiatry Neurol. 2010; 2010: 720958, PMID: 20862335; Journal of Neuropathology & Experimental Neurology. 61( 8). 2002. 736–744, DOI:10.1093/jnen/61.8.736; Front. Neurosci., 2019, DOI: 10.3389/fnins.2019.00463;