Another ISG15 substrate in the DDR pathway is the tumor suppressor phosphatase and tensin homolog (PTEN), which is lost in many cancer types (Lee et al., 2018; Alvarez-Garcia et al., 2019) and also plays important roles in diabetes (Li et al., 2017) and autism (Cummings et al., 2022). The gene discussed is ISG15; the disease is cancer.