Our study elucidated that CTGF promotes the repair and regeneration of alveoli after acute lung injury by promoting the proliferation of Krt5 expressing AEC2s in a LRP6-Wnt signaling pathway-dependent manner, which may shed light on the mechanism of lung tissue repair after ALI and provide a potential therapeutic target for ALI and ARDS. Here, CCN2 is linked to acute respiratory distress syndrome.