SynopsisProfilaggrin (proFLG) and its processing products are critical to the health and appearance of skin. The recent identification of loss‐of‐function filaggrin (FLG) mutations as a predisposing factor in ichthyosis vulgaris and atopic dermatitis has lead to a resurgent interest in this enigmatic protein. Here, we review the literature on the structure and many functions of proFLG, from its role as a filament‐aggregating protein and a source of natural moisturizing factor (NMF), to the more recent discoveries of its role in epidermal barrier formation and its more speculative functions as an antimicrobial and sunscreen. Finally, we discuss the relationship of proFLG with dry skin, the influence of moisturizers on NMF generation and speculate on next generation of FLG research.