They are also considered as damage-associated molecular pattern molecules (DAMPs), and knockdown of aryl hydrocarbon receptor downregulates the expression of S100 proteins in THP-1 cells.

In contrast, calmodulin is a ubiquitous and universal intracellular Ca2+ receptor widely expressed in many cells.

S100 proteins have been implicated in a variety of intracellular and extracellular functions,[6] such as regulation of protein phosphorylation, transcription factors, Ca2+ homeostasis, the dynamics of cytoskeleton constituents, enzyme activities, cell growth and differentiation, and the inflammatory response.

S100A7 (psoriasin) and S100A15 have been found to act as cytokines in inflammation, particularly in autoimmune skin conditions such as psoriasis.

The "S100" symbol prefix denotes that these proteins are soluble in 100%, i.e. saturated, ammonium sulfate at neutral pH.