TABLE 1.

Function and mechanism of LCN2 receptors.

Receptor	Function	Mechanism/Signaling pathway	References
24p3R	Cell proliferation	May mediate cell proliferation through gonadotropin independent or dependent manners	Donkor, 2018
		May mediate cell proliferation through Wnt/β-catenin signaling pathway	Ferdinand and Roffe, 2016
	Iron transportation	24p3R regulates iron uptake depend on the ligand: iron-loaded 24p3 and iron-lacking 24p3	Dixon et al., 2012; Miranda et al., 2019
	Cell apoptosis	Induce apoptosis via elevated Bim expression	Dixon et al., 2012; Doll and Conrad, 2017
		IL-3 deprivation promote synthesis and secretion of 24p3 through 24p3R, which induces apoptosis through an autocrine pathway	Du et al., 2021
		Runx3 activates 24p3R to promote apoptosis	Flower, 1996
		LCN2/LCN2R involves in METH-induced mitochondrion-related apoptosis	Chen et al., 2015
		May regulate apoptosis through TLR-4 signaling pathway	Ferdinand and Roffe, 2016
	Protein endocytosis	24p3R mediates albumin endocytosis through NF-κB and TGF-β1 signaling pathways	Egashira et al., 2014
		24p3R mediates protein endocytosis (unknown signaling)	Dyet et al., 2006; Dong et al., 2013; Du et al., 2019
	Whiter matter injury	Induce myelin damage, oligodendrocyte loss (unknown signaling)	Egashira et al., 2015
	Neuronal death	Induce neuronal death (unknown signaling)	Elneihoum et al., 1996; Fang et al., 2007; Feiler et al., 2011
	Ventricular dilation	Enlarge brain ventricle (unknown signaling)	Feiler et al., 2011
	Neuroinflammation	Induce neutrophil infiltration (Erk1/2), pro-inflammatory factors expression and glial activation	Elneihoum et al., 1996; Raymond et al., 2003; Feiler et al., 2011; Rathore et al., 2012; Egashira et al., 2015
	BBB disruption	Increase BBB permeability (unknown signaling)	Elneihoum et al., 1996; Egashira et al., 2015
	Neutrophil ability	MAPK/MEK1/2 signaling pathway	Rymer, 2011
Megalin	Development and cell proliferation	Mediate central nervous system development and cell proliferation (unknown signaling)	Gantz and Fong, 2003; Gu et al., 2009; Guo et al., 2014; Garg et al., 2015
	Regulate cubilin function	Form megalin/cubilin complex to regulate cubilin function	Garton et al., 2016; Gill et al., 2018; Gomes et al., 2020
	Protein endocytosis	Megalin regulate endocytosis of vitamin D, retinol, hemoglobin, insulin, albumin and drugs (unknown signaling)	Goetz et al., 2000, 2002; Gburek et al., 2002; Gill et al., 2018; Ghosh et al., 2020; Gomes et al., 2020
	Cell cycle	Mediate endothelial cell cycle via P13K/Akt signaling pathway	Hochmeister et al., 2016
	Transportation of small molecules	Promoted serum IGF-1 cross the choroid plexus barrier	Holland et al., 2018
MC4R	Anorexigenic progress	MC4R mediates anorexigenic progress through activating MSH	Holmes et al., 2005

METH, methamphetamine; MC4R, melanocortin-4-receptor gene; MSH, melanocyte-stimulating hormones.