Suprabasin (SBSN), a gene with initially unknown function, was originally described as a component of the cornified envelope. It is expressed in stratified epithelia. Three SBSN isoforms code for secreted proteins potentially acting as signalling molecules [1]. SBSN may be involved in human tumourigenesis as its expression is associated with poor prognosis in patients with oesophageal carcinoma, glioblastoma multiforme, and myelodysplastic syndromes [1]. It also plays a role in regulating normal epidermal barrier function [3].

SBSN-null mice showed skin barrier dysfunction on embryonic day 16.5, but normal barrier function after birth despite ultrastructural changes in stratum corneum and keratohyalin granules. These mice had higher blood nickel levels after oral nickel feeding and elevated contact hypersensitivity to nickel under nickel-loading condition, sharing features of intrinsic atopic dermatitis (AD) [5]. In SBSN-knockdown three-dimensional human living skin equivalent model, SBSN deficiency led to compact stratum corneum, immature stratum granulosum, and increased keratinocyte apoptosis, suggesting SBSN has an anti-apoptotic activity and its deficiency is involved in AD pathogenesis [6]. In bladder cancer, SBSN promotes invasion and metastasis through activation of the EGFR/SRC/STAT3 pathway [2]. In glioma, extracellular vesicles-transferred SBSN drives aggressiveness by activating NF-κB via ANXA1-dependent ubiquitination of NEMO [4].

In conclusion, SBSN plays a role in normal epidermal barrier regulation and is involved in multiple disease conditions such as AD, bladder cancer, and glioma. Gene-knockout mouse models have been crucial in revealing its function in these biological processes and disease states, providing insights into potential therapeutic targets.