Our study delves into the intricacies of nab-paclitaxel resistance in a model of pancreatic adenocarcinoma, PANC-1, and pinpoints the pivotal role played by three SAC proteins—BUB1B, TTK, and BUB3—in determining sensitivity of a pancreatic cancer cell line to paclitaxel. Here, TTK is linked to familial pancreatic carcinoma.