Contributes to various developmental events and other processes such as wound healing and cholesterol homeostasis through its interactions with multiple signaling pathways (PubMed:21856951, PubMed:22995554, PubMed:25159578, PubMed:31391339). Wnt signaling inhibitor which competes with WNT2B for binding to Wnt receptor FZD4 and represses WNT2B-dependent development of the peripheral eye (PubMed:21856951). Plays a role in regulating the hair cycle by controlling TGFB1 signaling (PubMed:22995554). Required for the development of the anterior commissure in the brain by inhibiting neurite outgrowth (PubMed:21055390, PubMed:23206892). Essential for terminal differentiation of hippocampal neural stem cells (PubMed:31983064). Plays a role in regulating bone elongation and bone mass by modulating growth plate chondrocyte function and overall body size (PubMed:30271858). Required for development of the inner ear through its involvement in stereocilia formation in inner hair cells (PubMed:32127020). Facilitates wound healing by inhibiting secretion of TGFB1 from macrophages which prevents myofibroblast differentiation, maintaining inflammatory cell quiescence (PubMed:25159578). Plays a role in cholesterol homeostasis by reducing circulating high-density lipoprotein cholesterol, lowering cholesterol efflux capacity and decreasing cholesterol-to-bile acid conversion in the liver (PubMed:31391339). In one study, shown to negatively regulate sympathetic innervation in brown fat, leading to reduced energy expenditure (PubMed:31535079). In another study, shown not to affect brown fat thermogenic capacity, body weight gain or glucose homeostasis (PubMed:31767170). Interacts with FZD4 (via FZ domain); competes with WNT2B for binding to FZD4, inhibiting Wnt signaling and repressing peripheral eye development (PubMed:21856951). Interacts with TGFB1; the interaction contributes to regulation of the hair cycle (PubMed:22995554). Interacts with netrin (PubMed:23206892). Interacts with CCN2 (PubMed:30232710). Expressed in macrophages in inflamed wounds with wound expression starting 2 days post-wounding (dpw) (at protein level) (PubMed:25159578). At 7 dpw, expressed from epidermis and extracellular matrix in the wound edge to neoepidermis and granulation tissue and in panniculus carnosus under the granulation tissue (at protein level) (PubMed:25159578). After fibrosis, disappears in the dermal area at 11 dpw (at protein level) (PubMed:25159578). Expressed in the hair follicle during morphogenesis and the hair cycle (at protein level) (PubMed:22995554). In embryonic brain, strong expression in the olfactory bulb, anterior olfactory nucleus, neocortex, piriform cortex, glial wedge, midline zipper glia, indusium griseum and the area surrounding the anterior commissure (AC) but not on AC axons (at protein level) (PubMed:23206892). In the adult eye, expressed in retinal layers, lens epithelium, and ciliary body where it is expressed predominantly in the inner non-pigmented layer (PubMed:21856951). Expressed in almost all brain regions in the embryo, in the cortex and the lateral ventricle at P0 and is restricted to the subventricular zone and lateral nucleus of the amygdala in adults (PubMed:21055390). Prominent expression in hippocampal regions from early postnatal stages until postnatal day 15 and gradually declines at later stages (PubMed:31983064). Expressed in almost all bone regions in the femurs of juveniles (PubMed:30271858). In the inner ear, accumulates in nonprosensory regions during early embryonic stages and in both nonprosensory and prosensory regions in late embryonic stages (PubMed:32127020). In the adult ear, expressed in the organ of Corti, spiral ganglion cells, and the stria vascularis (PubMed:32127020). Highly expressed in the liver where it is detected primarily in hepatocytes but not in non-parenchymal cells (PubMed:31535079). During the hair cycle, expression is down-regulated at the first telogen stage and is up-regulated at the secondary anagen stage. By endoplasmic reticulum stress and inflammation (PubMed:31391339). Up-regulated in response to high-fat diet and this is reversed by return to a normal diet (PubMed:30595550, PubMed:31391339). Expansion of the ciliary body and up-regulation of Wnt2b and Fzd4 expression in the developing peripheral eye (PubMed:21856951). Delayed hair cycle with down-regulation of Tgfb1 throughout the cycle and low levels of phosphorylated Smad2/3 (PubMed:22995554). Failure of the axons of the anterior and posterior parts of the anterior commissure (AC) to cross the midline, leading to an almost total absence of the AC in adults (PubMed:21055390, PubMed:23206892). Reduced size of hippocampus and dentate gyrus (DG), increased number of neural stem cells (NSCs) in the DG at P15, altered ratio of proliferating and quiescent NSCs with an increase in the number of proliferating NSCs in the DG at P15, and abnormal terminal differentiation of NSCs (PubMed:31983064). Decreased weight and short stature due to decreased longitudinal bone growth coupled with low bone mass (PubMed:30271858). Shortened and morphologically abnormal growth plates and abnormal expression of chondrogenic marker genes (PubMed:30271858). Formation of abnormally short and dislocated stereocilia in the inner hair cells of the ear and hearing loss (PubMed:32127020). Reduced cochlear expression of Sox2 and translocation of Sox2 from the nucleus to the cytoplasm in spiral ganglion cells (SGCs) at P0 (PubMed:32127020). Redistribution of Bmp4 with diminished expression in the outer sulcus and sparse distribution around the cochlear epithelium (PubMed:32127020). Reduced number of SGCs at the cochlear basal turn (PubMed:32127020). Excess wound inflammation with up-regulation of Tgfb1, Stat3 and Il6 during wound healing (PubMed:25159578). Reduced body size, increased levels of circulating high-density lipoprotein cholesterol and increased cholesterol efflux (PubMed:31391339). Some studues showed increased sympathetic innervation and norepinephrine release in adipose tissue, leading to enhanced adrenergic signaling and thermogenesis, attenuation of brown fat whitening and protection from diet-induced obesity (PubMed:31535079, PubMed:30595550). Another study found no effect on brown fat thermogenic capacity, protection from diet-induced obesity or glucose homeostasis (PubMed:31767170). Double knockout of Tsku and Draxi results in a higher frequency of AC defects than single knockout of either Tsku or Draxi (PubMed:23206892). This factor is named 'Tsukushi' because its expression pattern in chick embryos is similar to the shape of the Japanese horsetail plant, tsukushi.