Multiple divergent repeats work together to determine the spatial regulation of TPX2 activities and its preference for older MTs. (A) Model for the differential regulation of TPX2 activities at different spatial locations within the spindle. (1) In the vicinity of chromosomes, where the Ran-GTP concentration is high, TPX2 displays maximal MT-binding affinities and MT nucleation–promoting and stabilization activities. (2) Near the spindle poles, where the Ran-GTP concentration is low, MT nucleation–promoting and stabilization activities of TPX2 are limited due to the impeded function of R1-3 and R4 by importin α/β, while TPX2 can still bind MTs via R8-9. (B) Model for the mechanisms underlying TPX2’s preference for older MTs. The sequential binding and interplay between repeats with opposite preferences can alter the structure of MT lattices, allowing more TPX2-binding sites to form over time, ultimately leading to its bias toward older regions of GDP-MT lattices.