SHH and cancer: Hedgehog signaling drives growth during development and is reactivated in certain cancers, making HHAT an attractive therapeutic target to block aberrant signaling.[1] HHAT S‐acylates Hedgehog signaling proteins, which then undergo S,N‐acyl shift to yield the final amide‐linked product.[3] HHAT predominantly attaches palmitic (C16:0) fatty acid, using palmitoyl‐Coenzyme A (Pal‐CoA) as the lipid donor substrate (Figure 1 A).[3]N‐acylation of Sonic Hedgehog protein (SHH) by HHAT and C‐terminal auto‐O‐cholesterylation[10] is required for signaling function.