ALOX12B encodes arachidonate 12-lipoxygenase, 12R type, a key enzyme catalyzing the regio- and stereo-specific oxygenation of polyunsaturated fatty acids to generate lipid hydroperoxides and hydroxy species 1. In skin, ALOX12B acts upstream of ALOXE3 on linoleate moieties of esterified omega-hydroxyacyl-sphingosine ceramides to produce epoxy-ketone derivatives essential for conjugation of omega-hydroxyceramides to membrane proteins 1. This process is critical for corneocyte lipid envelope synthesis and establishing the skin barrier to water loss 2. Loss-of-function ALOX12B mutations represent the second most common cause of autosomal recessive congenital ichthyosis (ARCI), characterized by impaired epidermal barrier function and abnormal differentiation 34. To date, 88 pathogenic ALOX12B mutations have been reported, with missense and frameshift mutations accounting for 80% of cases 4. Beyond cutaneous manifestations, ALOX12B deficiency may trigger secondary immune dysregulation, including elevated IgE levels and increased susceptibility to infections, warranting multidisciplinary clinical evaluation 5. ALOX12B expression is also regulated by inflammatory cytokines in keratinocytes, linking its function to lipid barrier alterations in inflammatory skin diseases 6.