The mitotic delay of glc7-129 and glc7-10 mutants depends on the SAC. During mitosis, Glc7 has been described to oppose the kinase activity of Ipl1 by dephosphorylating the kinetochore proteins Ndc10 and Dam1, as well as histone H3. The correct balance of the Glc7 phosphatase and Ipl1 kinase activities ensures proper chromosome bi-orientation. According to the prevalent model, Ipl1 senses incorrect attachments lacking tension during metaphase and phosphorylates a AbMole Nodakenin critical kinetochore component, Dam1. Glc7 then reverses this modification and thereby allows microtubule attachment. This eventually leads to correct bi-polar attachment and cell cycle progression. Consequently, certain glc7 partial-loss-of-function alleles suppress the temperature sensitivity of hypomorphic ipl1 mutants by restoring the phosphatase to kinase balance. Shp1 has previously been implicated in the regulation of several cytosolic functions of Glc7. In this study, we identify the Cdc48Shp1 complex as a critical positive regulator of Glc7 activity towards mitotic Ipl1 substrates including Dam1. We show that shp1 mutants exhibit a SAC-mediated cell cycle delay resulting from reduced Glc7 activity, which in turn is caused by the lack of a specific Cdc48Shp1 function. Moreover, we provide evidence that Cdc48Shp1 regulates Glc7 activity by controlling its interaction with regulatory subunits rather than affecting Glc7 protein levels or localization. This study addresses the relationship of Shp1, a major Cdc48 cofactor, and Glc7, the catalytic subunit of budding yeast PP1. We found that shp1 mutants exhibit a variety of severe phenotypes, including a significant mitotic delay during progression from metaphase to anaphase. We were able to show that the mitotic phenotype of shp1 mutants is caused by limiting nuclear Glc7 activity towards mitotic substrates, resulting in their hyperphosphorylation due to unbalanced Ipl1 kinase activity. By engineering shp1 alleles specifically defective in Cdc48 binding, we established that Shp1 regulates Glc7 in its capacity as a Cdc48 cofactor. Importantly, we could demonstrate that Shp1 and Glc7 interact physically, and that the Cdc48Shp1 complex is required for normal interaction of Glc7 with Glc8. shp1 mutants were originally found to exhibit reduced Glc7 activity towards glycogen phosphorylase, decreased glycogen accumulation, and defective sporulation. Other shp1 phenotypes attributed to reduced Glc7 activity include defective vacuolar degradation of fructose-1,6-bisphosphatase through the vacuole import and degradation pathway, impaired V-ATPase activity, and impaired glucose repression. Here, we provide several lines of evidence that shp1 mutants also possesses a significant defect in mitotic Glc7 activity. First, the genetic interactions between shp1 and glc7, sds22, mad2, and ipl1 all point towards impaired nuclear function of Glc7 in shp1. Second, overexpression of GLC7 in shp1 restored a normal cell cycle distribution and suppressed chromosome segregation defects. Third, the nuclear Glc7 substrates histone H3 and Dam1 are hyperphosphorylated in shp1 in an Ipl1-dependent manner. Together with the previously described cytosolic and vacuolar processes, the elucidation of its involvement in mitotic Glc7 functions underscores the importance of Shp1 as a positive regulator of many, if not most, Glc7 functions. One likely explanation for the differences between the two studies relates to the strains used by Cheng and Chen.