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Updated: May 6, 2026

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Published on: February 24, 2026

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RILPL2 suppresses metabolic reprogramming and progression of cervical cancer by attenuating LDHA protein stability

Yujing Shi1, Zhaoyue Zhang2,3, Jin Liu2

  • 1Department of Oncology, Jurong hospital affiliated to Jiangsu university, Zhenjiang, Jiangsu province, China.

Cell Death & Disease
|May 4, 2026
PubMed

Insights

Rab-interacting lysosomal protein-like 2 (RILPL2) is downregulated in cervical cancer (CC), inhibiting tumor growth by targeting lactate dehydrogenase A (LDHA) and blocking glycolysis. This suggests RILPL2 as a potential therapeutic target for CC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cervical cancer (CC) is a significant global health concern.
  • Rab-interacting lysosomal protein-like 2 (RILPL2) is implicated as a tumor suppressor in various cancers.
  • The role of RILPL2 in cervical cancer pathogenesis is not well understood.

Purpose of the Study:

  • To investigate the role and mechanism of RILPL2 in cervical cancer.
  • To determine the relationship between RILPL2 expression and patient outcomes.
  • To explore RILPL2's interaction with key metabolic pathways in CC.

Main Methods:

  • Analysis of RILPL2 expression in CC tissues.
  • Investigation of RILPL2's interaction with lactate dehydrogenase A (LDHA).
  • Assessment of RILPL2's effect on glycolysis, protein ubiquitination, and downstream signaling pathways.

Main Results:

  • RILPL2 expression was found to be downregulated in CC samples, correlating with favorable outcomes.
  • RILPL2 was shown to interact with LDHA, reducing its stability through TRIM21-mediated K48-linked ubiquitination and degradation.
  • RILPL2 inhibited CC progression by blocking glycolytic reprogramming and downstream effects on H3K18 lactylation, SOX9, and SMYD2.

Conclusions:

  • RILPL2 functions as a tumor suppressor in cervical cancer.
  • The RILPL2/LDHA axis plays a critical role in regulating glycolysis and CC development.
  • RILPL2 represents a promising therapeutic target for cervical cancer treatment.

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