SPRR5 is a small proline-rich protein that positively regulates keratinocyte differentiation. Based on limited published evidence, SPRR5 functions as an essential positive regulator of epidermal homeostasis by inducing genes associated with epidermal differentiation 1. SPRR5 expression is repressed by the long non-coding RNA LINC00941, which itself acts as a repressor of keratinocyte differentiation, suggesting SPRR5 serves a critical role in the regulatory network controlling epidermal cell fate determination.