Researchers identified a genetic variant (rs1950834) that increases depression risk by reducing production of LRFN5, a protein important for brain connections. They found this variant affects how brain cells in a region called the nucleus accumbens produce LRFN5. When LRFN5 levels are low, mice become more depressed and sensitive to stress, but boosting LRFN5 protects against depression. This discovery could lead to new ways to diagnose and treat depression.