The skeletal muscle manifestations of Pompe disease (glycogen storage disease type II) are not successfully treated by the standard ERT (algucoside alfa, brand name Lumizyme; Sanofi).12,97 This is because both skeletal expression of CI-M6PR is low and the standard GAA ERT is not functionalized with much M6P.98,99 There have been a few different approaches to overcome this issue, including increasing the modification of the ERT with M6P, switching to other CI-M6PR targeting ligands, and targeting the enzyme through an orthogonal receptor. Here, IGF2R is linked to Glycogen storage disease due to acid maltase deficiency.