In our cohort, patients with likely pathogenetic variants of SAMD9L, particularly those in a compound heterozygous state, showed a combination of pulmonary arterial hypertension and ILD, suggesting that SAMD9L dysfunction may contribute to vascular damage, fibrosis, and chronic inflammation, all of which are central to SSc-ILD pathogenesis. Here, SAMD9L is linked to systemic sclerosis.