The biosynthesis of 3'-phosphoadenosine 5'-phosphosulfate (PAPS), a universal sulfate donor, is catalyzed by two isoenzymes: PAPS synthetase 1 (PAPSS1) and PAPS synthetase 2 (PAPSS2). While PAPSS1 is ubiquitously expressed, PAPSS2 shows tissue-specific expression and plays a key role in cartilage development and adrenal steroid metabolism. PAPSS2 deficiency impairs dehydroepiandrosterone sulfation (DHEA-S), leading to increased bioactive androgens and hyperandrogenism. Biallelic PAPSS2 variants cause skeletal dysplasias from brachyolmia (BO) to severe spondyloepimetaphyseal dysplasia (SEMD). This study aimed to expand the PAPSS2 mutational spectrum and explore potential genotype-phenotype correlations, including the distribution of variants across functional domains.