ASPH and neoplasm: Our study elucidated the heterogeneous responses of various tumor cell lines to ASPH inhibition, which are mediated either by suppressing the activation of the Notch1 receptor, resulting in a reduction in NICD translocation to the nucleus and downregulation of downstream targets of the canonical Notch1 pathway, or by affecting the noncanonical Notch1 pathway by targeting AKT phosphorylation.