PIERCE1 (piercer of microtubule wall 1) has dual functions in ciliary biology and cellular stress responses. As a microtubule inner protein, PIERCE1 is essential for outer dynein arm attachment to axonemal doublet microtubules, which is critical for motile cilia beating and left-right asymmetry specification 1. This ciliary function is reflected in its role during ciliogenesis, where PIERCE1 expression is downregulated during primary cilium formation 2. In cellular stress responses, PIERCE1 functions as a p53 target gene involved in DNA damage response. UVC irradiation induces PIERCE1 expression via p53 activation, and ATR signaling stabilizes PIERCE1 protein post-translationally 3. PIERCE1 knockdown impairs checkpoint response to UV damage, indicating its importance for genomic integrity. However, p53-responsiveness of PIERCE1 diverges significantly between species due to differences in promoter architecture—p53-responsive elements are conserved in mice but not humans 4. Regarding cancer relevance, PIERCE1 demonstrates context-dependent roles. In KRAS-mutant non-small cell lung cancer, PIERCE1 promotes tumor growth by suppressing TRIB3 expression through the CHOP pathway, thereby enhancing AKT signaling 5. Conversely, PIERCE1 shows no oncogenic or tumor-suppressive function in AOM/DSS-induced colorectal cancer 6. These findings suggest PIERCE1's role in tumorigenesis is mutation-context dependent rather than universally oncogenic.