CTCF (CCCTC-binding factor) instructs 3D genome folding by anchoring or forestalling cohesin loop extrusion, but the exact mechanism remains obscure. Here, using clustered protocadherins (cPcdh) as model genes, we report that CTCF assists or facilitates cohesin loop extrusion by enhancing its processivity. Specifically, we show that, compared with the Pcdh α and γ gene clusters, the Pcdhβ cluster is greatly affected upon CTCF