ARSL (arylsulfatase L) is an X-linked gene encoding an arylsulfatase enzyme that exhibits catalytic activity toward artificial sulfate substrates like 4-methylumbelliferyl sulfate 12, but lacks activity toward steroid sulfates 1. The enzyme is essential for correct composition of cartilage and bone matrix during skeletal development 1. ARSL localizes to the endoplasmic reticulum lumen and Golgi apparatus, functioning in extracellular contexts [GO annotations]. Loss-of-function variants in ARSL cause X-linked recessive chondrodysplasia punctata 1 (CDPX1), a rare congenital skeletal dysplasia characterized by stippled epiphyses, nasal hypoplasia, brachydactyly, and shortened long bones 34. Prenatal manifestations include bony stippling (41% of cases), nasal hypoplasia (55%), shortened long bones (23%), and intrauterine complications including fetal death and intraventricular hemorrhage 3. Genetic heterogeneity presents diagnostic challenges; prenatal diagnosis relies on whole exome sequencing and molecular confirmation 4. Notably, maternal X-chromosome X disomy can cause CDPX1 in females through homozygosity of pathogenic ARSL variants, representing an atypical inheritance mechanism 5. These findings underscore ARSL's critical role in skeletal development and establish it as the primary genetic determinant of CDPX1.