One of the most well-known physiological roles of HTRA1 is its ability to cleave numerous ECM proteins, including EFEMP1 and C1QTNF5/CTRP5 that are involved in monogenic retinal degenerative diseases such as Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD) (20) and late-onset retinal degeneration (L-ORD) (21), respectively. Here, C1QTNF5 is linked to late-onset retinal degeneration.