Sterol 14-reductase (ERG24)

Sterol 14-reductase, primarily encoded by the ERG24 gene in fungi, is a critical enzyme in the ergosterol biosynthetic pathway (1, 5). It catalyzes the NADPH-dependent reduction of the C14-C15 double bond in sterol intermediates such as 4,4-dimethylcholesta-8,14,24-trien-3β-ol (10). Because ergosterol is an essential component of fungal cell membranes, maintaining its synthesis is vital for fungal viability, growth, and virulence (3, 9). Inhibition of this enzyme leads to the depletion of ergosterol and the accumulation of ignosterol, which destabilizes the cell membrane and impairs vacuolar function and ion homeostasis (4, 6). This enzyme is the primary target for the morpholine class of antifungal agents, including amorolfine, which is widely used to treat superficial fungal infections like onychomycosis (2, 11). While highly effective against fungi, the potential for cross-reactivity with human orthologs like the Lamin B Receptor (LBR) has largely restricted the clinical use of its inhibitors to topical formulations (14, 15).

Other names

Delta(14)-sterol reductaseC-14 sterol reductaseErg24pSterol C14-reductaseC14R

Inhibition of the enzyme prevents the NADPH-dependent reduction of the C14-C15 double bond in sterol intermediates, leading to the depletion of ergosterol and the accumulation of the atypical sterol ignosterol, which disrupts fungal cell membrane integrity and vacuolar function.