Timp1, also known as tissue inhibitor of metalloproteinases-1, is named for its well-established function of inhibiting the proteolytic activity of matrix metalloproteases. It can also modulate cell behavior through the induction of signaling pathways involved in cell growth, proliferation, and survival. TIMP1 is associated with many biological processes and diseases, and genetic models are valuable for studying its functions [5].

In pancreatic cancer, TIMP1 triggers neutrophil extracellular trap (NET) formation. In genetically engineered PDAC-bearing mice, abrogation of TIMP1 prolonged survival, indicating its role in promoting cancer progression through NET formation [1]. In pancreatic cancer cell-Schwann cell interaction, TIMP1 knockdown in PDAC cells suppressed perineural invasion (PNI), suggesting that TIMP1 promotes PNI through a paracrine feedback loop with CCL7 [2]. In thyroid cancer, inhibiting TIMP1 expression reduced the malignant biological traits of PTC cells and impeded M2 macrophage polarization [3]. In subarachnoid haemorrhage, TIMP1 mitigated early brain injury by protecting the blood-brain barrier integrity through regulating astrocytic β1-integrin [4]. In type 2 diabetic osteoporosis, suppression of TIMP1 expression alleviated osteoporosis progression as TIMP1 promotes ferroptosis in osteoblasts [6]. In colorectal cancer, TIMP1 can be used as a biomarker, and its expression is associated with the immunological microenvironment, drug sensitivity, and ferroptosis inhibition [7]. In thyroid cancer, HHT inhibits cancer progression by down-regulating TIMP1 and inactivating the FAK/PI3K/AKT signaling pathway [8]. In gastric cancer, TIMP1 expression is related to tumor differentiation and poor prognosis [9].

In conclusion, Timp1 plays diverse and crucial roles in multiple biological processes and diseases. The use of gene knockout or conditional knockout mouse models has significantly contributed to understanding its functions in areas such as cancer progression, neural invasion in pancreatic cancer, macrophage polarization in thyroid cancer, blood-brain barrier protection after subarachnoid haemorrhage, osteoporosis in type 2 diabetes, and biomarker discovery in colorectal and gastric cancers. These findings provide valuable insights into the underlying mechanisms of diseases and potential therapeutic targets.