Steroid sulfatase (STS) is an X-linked enzyme located at Xp22.3 that catalyzes the hydrolysis of sulfated steroid precursors, converting dehydroepiandrosterone sulfate (DHEA-S) and estrone sulfate to their unconjugated forms 1. As a calcium-dependent integral membrane protein of the endoplasmic reticulum, STS plays a critical role in maintaining the balance between androgens and estrogens by generating precursors for the most potent steroid hormones, including 17β-estradiol, estriol, testosterone, and dihydrotestosterone 1. STS deficiency causes X-linked ichthyosis (XLI), the second most common ichthyosis type (prevalence 1/6,000-1/2,000 in males) 2. Loss-of-function mutations in STS lead to abnormal accumulation of cholesterol sulfate in the stratum corneum, disrupting the epidermal permeability barrier and causing generalized skin dryness, scaling, and extracutaneous manifestations 2. Beyond dermatological significance, STS functions in multiple tissues including reproductive and central nervous systems, where local enzyme expression maintains elevated reproductive steroid levels critical for endocrine function 1. Understanding STS pathogenic variants is essential for accurate clinical diagnosis and developing novel therapeutic strategies for ichthyosis and potentially other steroid hormone-related disorders.